Inflammation is usually beneficial Flashcards
What is inflammation?
It is the tissue response to injury or infection, characterised by an increase in blood flow, swelling, elevated temperature, pain and redness.
Name a key component of inflammation
The complement system
What is the complement system?
A set of ~20 or more different proteins which act in an enzymic amplification cascade system to generate a number of active complement components (small signal, large response) involved in several aspects of the immune response. These are soluble molecules released by cells and receptors.
Where is the complement system synthesised?
By the liver and macrophages (the main two)
What is a zynogen?
An inactive form of an enzyme which can be cleaved and split to form the active form of the enzyme.
What are the three complement pathways?
Classical, lectin and Alternative
Which are the two most similar complement pathways?
Classical and lectin
How is the classical pathway activated?
By immune complexes Ab-Ag
What is C1-INH
It is the complement component c1 inhibitor which regulates the activation of c1.
Which component of the classical and lectin pathway has C3 convertase activity?
C4b2a
Which component of the classical and lectin pathway has C5 convertase activity?
C4b2a3b
What is the common end point of the classical and lectin pathway?
C5 is splitting into C5a and C5b. C5b then binds to C6-9 to form the membrane attack complex (MAC)
How does the lectin pathway differ from the classical?
The lectin pathway is activated by surface carbohydrates of bacterial cell walls. Lectin is a protein that binds carbohydrates. An example of a lectin is mannose binding lectin (MBL).
How is the alternative pathway activated?
by components of microbial cell surfaces, not carbohydrates, more protein based.
Which component of the alternative pathway has C3 convertase activity?
C3bBb
Which component of the alternative pathway has C5 convertase activity?
C3bBb3b
What is the universal common stage of complement activation?
The splitting of C3 into C3a and C3b.
What binds to C3b to give it it’s C3 convertase activity?
factor B
True or false: components of the complement system before the cleavage of C3 have immunological or physiological activity?
False, they no not have these activities until C3 is cleaved. Autocatalysis of C3 occurs minimally.
Which complement components are involved in immune responses?
C3a, C3b, C5a and MAC. These are not present in high levels where there is not an infection but are amplified in infection.
Which complement components stimulate mast cells?
C3a, C5a and C4a (Former two more so), mast cells are located in mucosal and connective tissue and release granules (degranulation) containing inflammatory mediators.
What does C5a do?
neutrophil chemotaxis
What does C3b and C4b do?
opsonisation (decreasing the likelihood of no recognition of the pathogen), C3b also clears immune complexes
What does C5b-C9
cell lysis (MAC)
What does C3d do?
B-cell activation, arises from C3a and C3b splitting.
How do our own cells prevent against the harmful effects of complement?
Through the expression of surface inhibitory proteins CD55 and CD59
How does the MAC operate?
Produces lytic complex on microbial cell membranes; deposition of C5 convertase on pathogen surface, C3bBb3b (or equivalent in classical/lectin) cleaves C5. C5b remains on cell surface. C6 and 7 insert partly into membrane. C8 penetrates cell membrane. C5b+6+7+8 act as catalysts for the polymerisation of several different C9 molecules which will insert into the membrane and polymerise to forma pore like strucuture inducing osmotic shock.
What does inflammation involve?
inflammatory mediators released from tissue mast cells (degranulation via PAMPs/tissue damage and becomes activated.
What are the two outcomes of mast cell activation?
i) release of granules to outside of mast cells; degranulation. Granules contain vasoactive amines (histamine), cytokines and chemokines.
ii) Activation of enzymes; Phospholipase A2 activation-Arachidonic acid pathway of 2 subpaths;
1) Lipoxygenase pathway resulting in leukotrienes; inflammatory mediators
2) cyclo-oxygenase pathway = prostaglandins - inflammatory mediators.
Describe the process of extrovasion of neutrophils;
Chemotaxis of circulating cells to infected tissues; neutrophils are the main cell (70%) and attracted by C5a. Enhanced vascular permeability facilitates chemotaxis. Neutrophils adhere to vascular endothelium through adhesion molecules such as E-selectin on endothelium binding to CD15 on neutrophils (glycosylated transmembrane adhesion proteins) causing rolling along blood vessel wall and induces expression of other adhesins; integrins of neutrophils which binds to ICAM-1 also has induced expression by LPS, TNF, IL-1 (positive feedback). In response to activating substances released by infectious agent and damage tissue causes E-selectin production. Once adhesion is achieved, diapedesis through the vascular endothelium and basement membrane occur; access to infection site.
